The architecture of the endoplasmic reticulum (ER) consists of an intricate network of sheets and tubules, but how these domains are generated remains largely unknown. The reticulons and reticulon-like proteins are needed to shape the ER. We have identified proteins with reticulon homology domains the ER in yeast and in higher eukaryotes. These proteins localize to subdomains in the ER in both yeast and mammalian cells. The subdomains are sites of biogenesis of lipid droplets (lipid storage depots) and pre-peroxisomes. Interestingly, the domains are also found at some membrane contact sites, regions where the ER comes in close contact with other organelles. In a second project, we are investigating the role of reticulon-like proteins called Pex30 in yeast and MCTP in higher eukaryotes, that localize to specialized subdomains of the ER where pre-peroxisome and lipid droplet biogenesis occur. We are investigating how they domains form and are regulated. We have also have evidence that the domains are often in contacts with other organelles and may regulate interorganelle communication.